The purpose of this core is to provide a phenotypic validation of the genetic manipulations made under the various projects. This core will provide neurobiological evaluations of trangenic and transonic lines constructed to provide overexpression of single or multiple genes from the Down syndrome region of human chromosome 21 or their murine counterparts. Behavioral, neurochemical and histological studies will be carried out to identify the specific neurobiological effects of overexpression of these genes to determine what genes singly or in combination with others may account for the mental retardation or other neurobiological outcomes exhibited in Down syndrome. The behavioral screens will include assessment of sensory and motoria development in neonatal animals, spontaneous locomotor activity in adults, and testing of aspects of learning and memory in both neonates and adults using conditioning paradigms and assessments of the animal's ability to acquire spatial discriminations and form learning sets. Brains will be screened for potential alterations in aspects of synaptic neurochemistry including assessments of norepinephrine, dopamine, serotonin and cholinergic transmission. Brains of trangenic and transonic animals will also be screened for neuropathological signs consistent with Down syndrome. These screens will include developmental and crossectional assessments of the presence of neuritic plaques, changes in synapse numbers and effects on specific synaptic membrane proteins neurofilament proteins and markers for synaptic transmitter. This Core will serve 3 of the 4 projects and provide assessments of the neurobiological outcomes of the specific manipulations proposed in those projects.